Cancer remains a major public health challenge despite progress in detection and therapy. Whole blood, serum, plasma, or nipple aspirate fluid are the most widely used sources of sample in clinical routine. Conventionally, researchers try to find valuable markers from plasma/serum to detect liver cancer. However, up to 90 percentage of the plasma/serum are composed by 6 constant serum proteins, and 99 percentage are composed by about 20 constant proteins. The metabolic and the physiological conditions could be represented in whole blood, serum or plasma. Some specific proteins with diagnosis values are secreted into whole blood, serum or plasma, but they always present in a trace amount and are hard to be found. Therefore, an urgent clinical need exists to improve the method to identify biomarkers for the diagnosis of liver cancer from plasma/serum.
Some researchers tried to find tumor markers from hepatocellular carcinoma (hereinafter may be referred to as “liver cancer”, “hepatoma” or “HCC”) tissue or cell culture media. However, neither tumor tissues nor cell culture media of hepatocellular carcinoma has been proved to be an adequate source for identifying new serum markers for hepatoma. In contrast, the tissue interstitial fluid is the media between tumor cells and the circulation, and tumor interstitial fluid represents the microenvironment that tumor cells inhabit. Tumor markers shed into circulation may also be generated by interaction of tumor cells with its microenvironment. It is, therefore, tempting to examine whether tumor interstitial fluid is the source for discovery of serum biomarkers.
So far, some markers, including alpha-fetoprotein (AFP), alpha-fetoprotein lectin fraction-L3 fraction, PIVKA-II, AFU and GPC3, have conventionally been employed for liver cancer diagnosis. However, results obtained from detecting by the foregoing tumor markers often show false-positive or false-negative, so that their functions of detection are limited clinically. Despite the large and ever growing list of candidate protein markers in the field of liver cancer, to date clinical/diagnostic utility of these molecules is not known. In order to be of clinical utility, a new diagnostic marker as a single marker should be at least as good at the best single marker known in the art. Or, a new marker should lead to a progress in diagnostic sensitivity and/or specificity either if used alone or in combination with one or more other markers, respectively.
Therefore, there is a keen need in the art to develop a new tumor marker for clinical diagnosis and increase the precision of diagnosis. It was the task of the present invention to investigate whether a new marker can be identified which may aid in liver cancer diagnosis. Surprisingly, it has been found that use of the marker ERBB3 or IGFBP2 can at least partially overcome the problems known from the state of the art.